The public health significance of many medical, psychiatric, and neurological conditions and/or disorders is often overlooked, probably because of their episodic nature and the lack of mortality attributed to them. However, some medical conditions, such as headaches and facial pain, are often incapacitating, with considerable impact on social activities and work, and may lead to significant consumption of drugs.
The International Headache Society (IHS) published “Classification and Diagnostic Criteria for Headache Disorders, Cranial Neuralgias and Facial Pain” in 1988. IHS identified 13 different general groupings of headache, given below in Table 1.
TABLE 1Groupings of Headache Disorders and Facial Pain1)Migraine2)Tension-type headache3)Cluster headache and chronic paroxysmal hemicrania4)Miscellaneous headaches unassociated with structural lesions5)Headache associated with head trauma6)Headache associated with vascular disorders7)Headache associated with non-vascular intracranial disorder8)Headache associated with substances or their withdrawal9)Headache associated with non-cephalic infections10)Headaches associated with metabolic disorders11)Headache or facial pain associated with disorder of cranium,neck, eyes, ears, nose, sinuses, teeth, mouth or other facialor cranial structures12)Cranial neuralgias, nerve trunk pain and deafferentation pain13)Non-classifiable headache
The IHS classification of the most common types of headache is summarized in Table 2 below.
TABLE 2IHS Classification of Primary Headaches1.Migraine1.1Migraine without aura1.2Migraine with aura1.2.1Migraine with typical aura1.2.2Migraine with prolonged aura1.2.3Familial hemiplegic migraine headache1.2.4Basilar migraine1.2.5Migraine aura without headache1.2.6Migraine with acute onset aura1.3Ophthalmoplegic migraine1.4Retinal migraine1.5Childhood periodic syndromes that may be precursors to orassociated with migraine1.5.1Benign paroxysmal vertigo of childhood1.5.2Alternating hemiplegia of childhood1.6Complications of migraine1.6.1Status migrainosus1.6.2Migrainous infarction1.7Migrainous disorder not fulfilling above criteria2.Tension-type headache2.1Episodic tension-type headache2.1.1Episodic tension-type headache associated with disorder ofpericranial muscles2.1.2Episodic tension-type headache not associated with disorder ofpericranial muscles2.2Chronic tension-type headache2.2.1Chronic tension-type headache associated with disorder ofpericranial muscles2.2.2Chronic tension-type headache not associated with disorder ofpericranial muscles2.3Headache of the tension-type not fulfilling above criteria3.Cluster headache and chronic paroxysmal hemicrania3.1Cluster Headache3.1.1Cluster headache, periodicity undetermined3.1.2Episodic cluster headache3.1.3.Chronic Cluster Headache3.1.3.1Unremitting from onset3.1.3.2Evolved from episodic3.2Chronic paroxysmal hemicrania3.3Cluster headache-like disorder not fulfilling above CriteriaMigraine Headache
The IHS classification provides diagnostic criteria for migraine without and with aura, summarized in Tables 3 and 4 below.
TABLE 3IHS Diagnostic Criteria for Migraine Without AuraA. At least five attacks fulfilling B-D below:B. Headache attacks lasting 4-72 hours (untreated or unsuccessfullytreated)C. Headache has at least two of the following characteristics:1.Unilateral location2.Pulsating quality3.Moderate or severe intensity (inhibits or prohibits daily activities)4.Aggravation by walking stairs or similar routine physical activityD. During headache at least one of the following:1.Nausea and/or vomiting2.Photophobia and phonophobiaE. At least one of the following:1.History and physical do not suggest headaches secondary to organicor systemic metabolic disease2.History and/or physical and/or neurologic examinations do suggestsuch disorder, but is ruled out by appropriate investigations3.Such disorder is present, but migraine attacks do not occur forthe first time in close temporal relation to the disorder
TABLE 4IHS Diagnostic Criteria for Migraine With AuraA. At least two attacks fulfilling B below:B. At least three of the following four characteristics:1.One or more fully reversible aura symptoms indicating focalcerebral cortical and/or brain stem dysfunction2.At least one aura symptom develops gradually over more thanfour minutes or two or more symptoms occur in succession3.No aura symptom lasts more than 60 minutes. If more than oneaura symptom is present, accepted duration is proportionallyincreased4.Headache follows aura with a free interval of less than 60 minutes.It may also begin before or simultaneously with the aura.C. At least one of the following:1.History and physical and neurologic examinations do not suggestheadaches secondary to organic or systemic metabolic disease2.History and/or physical and/or neurologic examinations do suggestsuch disorder, but it is ruled out by appropriate investigations3.Such disorder is present, but migraine attacks do not occur forthe first time in close temporal relation to the disorder
The IHS classification includes several different types of migraine variants. Basilar migraine is defined as a migraine with an aura involving the brainstem. Symptoms include ataxia, dysarthria, vertigo, tinnitus and/or changes in consciousness and cognition. Ophthalmoplegic migraine is associated with acute attacks of third nerve palsy with accompanying dilation of the pupil. In this setting, the differential diagnosis includes an intracranial aneurysm or chronic sinusitis complicated by a mucocele. The ophthalmoplegia can last from hours to months. Hemiplegic migraine is distinguished by the accompanying hemiplegia, which can be part of the aura, or the headache may precede the onset of hemiplegia. Hemiplegic migraine can be familial and may last for days or weeks, clinically simulating a stroke. An additional differential diagnosis includes focal seizures.
Status migrainosus describes a migraine lasting longer than 72 hours with intractable debilitating pain, and typically occurs in a setting of inappropriate and prolonged use of abortive anti-migraine drugs. These patients may require hospitalization, both for pain control, detoxification from the abused drugs, and treatment of dehydration resulting from prolonged nausea and vomiting.
A migraine prevalence survey of American households was conducted in 1992, and included 20,468 respondents 12-80 years of age. Using a self-administered questionnaire based on modified IHS criteria, 17.6% of females and 5.7% of males were found to have one or more migraine headaches per year. A projection to the total US population suggests that 8.7 million females and 2.6 million males suffer from migraine headache with moderate to severe disability. Of these, 3.4 million females and 1.1 million males experience one or more attacks per month. Prevalence is highest between the ages of 25 and 55, during the peak productive years.
Based on published data, the Baltimore County Migraine Study, MEDSTAT's MarketScan medical claims data set, and statistics from the Census Bureau and the Bureau of Labor Statistics, it has been estimated that migraineurs require 3.8 bed rest days for men and 5.6 days for women each year, resulting in a total of 112 million bedridden days. Migraine costs American employers about $13 billion a year because of missed workdays and impaired work function—close to $8 billion is directly due to missed workdays. Patients of both sexes aged 30 to 49 years incurred higher indirect costs compared with younger or older employed patients. Annual direct medical costs for migraine care are about $1 billion, with about $ 100 spent per diagnosed patient. Physician office visits account for about 60% of all costs; in contrast, emergency department visits contribute less than 1% of the direct costs.
Tension-Type Headache
The diagnostic criteria for tension-type headaches are summarized in Table 5 below. However, migraine symptoms may overlap considerably with those of tension-type headaches. Tension-type headaches are believed by some experts to be a mild variant of migraine headache. Patients with tension-type headaches who also have migraines may experience nausea and vomiting with a tension headache, though when they do, it typically is mild and for a shorter duration compared to that with a migraine. Tension-type headache may be a disorder unto itself in individuals who do not have migraines, and may manifest as attacks of mild migraine in individuals with migraines.
TABLE 5IHS Criteria for Various Forms of Tension-Type HeadacheTension-type headacheAt least two of the following pain characteristics:1.Pressing/tightening (non-pulsating) quality2.Mild or moderate intensity (may inhibit, but does notprohibit activities)3.Bilateral location4.No aggravation by walking stairs or similar routinephysical activityBoth of the following:1.No nausea or vomiting (anorexia may occur)2.Photophobia and phonophobia absent, or only one is presentAt least one of the following:1.History and physical do not suggest headaches secondaryto organic or systemic metabolic disease2.History and/or physical and/or neurologic examinations dosuggest such disorder, but is ruled out by appropriateinvestigations3.Such disorder is present, but tension-type headache doesnot occur for the first time in close temporal relation tothe disorderEpisodic tension-type headache (ETTH)Diagnostic criteria:A.At least 10 previous episodes, <180 days/year (<15/mo) withheadacheB.Headache lasting from 30 minutes to 7 daysChronic tension-type headache (CTTH)Diagnostic criteria:A.Average frequency ≧1 day/month (≧189 days/year) for ≧6 monthsTension-type headache associated with disorder of pericranial musclesAt least one of the following:1.Increased tenderness of pericranial muscles demonstrated bymanual palpation or pressure algometer.2.Increased electromyographic level of pericranial muscles atrest or during physiologic tests.Tension-type headache not associated with pericranial muscle disorderNo increased tenderness of pericranial muscles. If studied, electro-myography of pericranial muscles shows normal levels of activity.
Based on a telephone survey of 13,345 people, the 1-year period prevalence of episodic tension-type headache (ETTH) is estimated to be 38.3%, according to IHS criteria. Women had a higher 1-year ETTH prevalence than men in all age, race, and education groups, with an overall prevalence ratio of 1.16. Prevalence peaked in the 30- to 39-year-old age group in both men (42.3%) and women (46.9%). Prevalence increased with increasing educational levels in both sexes, reaching a peak in subjects with graduate school educations of 48.5% for men and 48.9% for women. Of subjects with ETTH, 8.3% reported lost workdays because of their headaches, while 43.6% reported decreased effectiveness at work, home, or school.
Chronic Daily Headache
Chronic tension-type headache (CTTH) is a subtype of tension headaches, with patients experiencing headaches daily or almost every day. In practice, the term “chronic daily headache” is commonly used to describe headaches lasting for greater than 4 hours per day and for at least 15 days per month. The classification of chronic daily headaches is summarized below in Table 6.
TABLE 6Classification of Chronic Daily HeadacheTransformed migraine1. With medication overuse2. Without medication overuseChronic tension-type headache (CTTH)1. With medication overuse2. Without medication overuseNew daily persistent headache1. With medication overuse2. Without medication overuseHemicrania continua1. With medication overuse2. Without medication overuse
In the study of 13,345 people cited above, the 1-year period prevalence of chronic tension-type headache (CTTH) was estimated to be 2.2%. This prevalence was higher in women and declined with increasing education. Subjects with CTTH reported more lost workdays (mean of 27.4 days vs. 8.9 days for those reporting lost workdays) and reduced-effectiveness days (mean of 20.4 vs. 5.0 days for those reporting reduced effectiveness) compared with subjects with ETTH.
Chronic daily headaches are best conceptualized as an umbrella category term referring to a group of headache disorders characterized by headaches which occur greater than 15 days per month, with an average untreated duration of greater than 4 hours per day. There are many secondary causes of chronic daily headache, including post-traumatic headache, arthritis, intracranial mass lesions, etc. There are also short-lived primary headache disorders that occur greater than 15 days per month, such as chronic cluster headache or the paroxysmal hemicranias. The most common primary, chronic daily headache disorders include transformed migraine, chronic tension-type headaches, new daily persistent headache, or hemicrania continua. Each of these diagnoses can be complicated by medication overuse (e.g., barbiturates, acetaminophen, aspirin, caffeine, ergotamine tartrate and opioids). When used daily, all of these medications can lead to a vicious cycle of rebound headaches.
Cluster Headache
The 1988 IHS classification system recognized the uniqueness of cluster headache as a clinical and epidemiological entity. Formerly classified as a vascular migraine variant, cluster headache (a.k.a. suicide headache) is thought to be one of the most severe headache syndromes. It is characterized by attacks of severe pain, generally unilateral and orbital and lasting 15 minutes to 3 hours, with one or more symptoms such as unilateral rhinorrhea, nasal congestion, lacrimation, and conjunctival injection. In most patients, headaches occur in episodes, generally with a regular time pattern. These “cluster periods” last for weeks to months, separated by periods of remission lasting months to years. These headaches primarily affect men and in many cases patients having distinguishing facial, body, and psychological features. Several factors may precipitate cluster headaches, including histamine, nitroglycerin, alcohol, transition from rapid eye movement (REM) to non-REM sleep, circadian periodicity, environmental alterations, and change in the level of physical, emotional, or mental activity. The IHS classification system gives specific diagnostic criteria for cluster headache, as given in Table 7 below.
TABLE 7IHS Diagnostic Criteria for Cluster Headache3.1 Cluster HeadacheA. At least 5 attacks fulfilling B-D below:B. Severe unilateral, orbital, supraorbital and/or temporal painlasting 15-180 minutes untreatedC. At least one of the following signs present on the pain side:1.Conjunctival injection2.Lacrimation3.Nasal congestion4.Rhinorrhea5.Forehead and facial sweating6.Miosis7.Ptosis8.Eyelid edemaD. Frequency of attacks: from 1 every other day to 8 per dayE. At least one of the following:1.History, physical and neurological examinations do not suggestone of the disorders listed in groups 5-11 of Table 12.History and/or physical and/or neurological examinations dosuggest such disorder, but it is ruled out by appropriateinvestigations3.Such disorder is present, but cluster headache does not occurfor the first time in close temporal relation to the disorder3.1.1 Cluster headache periodicity undefinedA. Criteria for 3.1 fulfilledB. Too early to classify as 3.1.2 or 3.1.33.1.2 Episodic cluster headacheDescription: Attacks lasting between 1 week and 3 months occurin periods lasting 1 week to one year separated by pain freeperiods lasting 14 days or more.A. All the letter headings of 3.1B. At least 2 periods of headaches (cluster periods lasting(untreated) from 7 days to one year, separated by remissionsof at least 14 days.3.1.3 Chronic cluster headacheDescription: Attacks lasting between 2 weeks and 3 months occurfor more than one year without remission or with remissionslasting less than 14 days.A. All the letter headings of 3.1B. Absence of remission phases for one year or more or withremissions lasting less than 14 days.3.1.3.1 Chronic cluster headache unremitting from onsetA. All the letter headings of 3.1.3B. Absence of remission periods lasting 14 days or more from onset.3.1.3.2 Chronic cluster headache evolved from episodicA. All the letter headings of 3.1.3B. At least one interim remission period lasting 14 days or morewithin one year after onset, followed by unremitting coursefor at least one year.
The estimated prevalence of cluster headache is 69 cases per 100,000 people. Men are affected more commonly than women in a proportion of 6:1. Although most patients begin experiencing headache between the ages of 20 and 50 years (mean of 30 years), the syndrome may begin as early as the first decade and as late as the eighth decade.
Cervicogenic Headache
Cervicogenic headache (CEH) is a headache with its origin in the neck area. The source of pain is in structures around the neck that have been damaged. These structures can include joints, ligaments, muscles, and cervical discs, all of which have complex nerve endings. When these structures are damaged, the nerve endings send pain signals up the pathway from the upper nerves of the neck to the brainstem. These nerve fibers may synapse in the same brainstem nuclei as the nerve fibers of the trigeminal nerve. Since the trigeminal nerve is responsible for the perception of head pain, the patient experiences the symptoms of headache and/or facial pain.
While many patients who are diagnosed with CEH have the traditional symptoms of tension-type headache, some of the patients who have the traditional symptoms of migraine and cluster headache also respond to CEH diagnosis and treatment.
Facial Pain
Facial pain may be due to a number of underlying disorders. Among the most common is Trigeminal Neuralgia (also known as tic douloureux). More than 50,000 people in the United States suffer from trigeminal neuralgia. This disorder may cause episodes of intense, stabbing, electric shock-like pain in the areas of the face where the branches of the nerve are distributed (e.g., the lips, eyes, nose, scalp, forehead, upper jaw, and lower jaw). A less common form of the disorder, Atypical Trigeminal Neuralgia, may cause less intense, constant, dull burning or aching pain, sometimes with occasional electric shock-like stabs. Both forms of the disorder most often affect one side of the face, but some patients experience pain at different times on both sides. Onset of symptoms occurs most often after age 50, and it affects women more often than men. For patients with this disorder, an ordinary touch of the face, such as when brushing teeth or applying makeup, can trigger an attack. Trigeminal neuralgia is believed to be due to hyper-excitability of fibers of the trigeminal nerve or its ganglion. Microelectrode recordings from the trigeminal ganglion have demonstrated sustained high-frequency bursts during pain episodes of trigeminal neuralgia.
Trigeminal neuralgia may be treated medically with drugs that decrease neural excitability, e.g., carbamazepine or phenytoin. However, such medications prove ineffective for many patients over the course of the disease. Thus, a number of surgical interventions (e.g., microvascular decompression of the trigeminal ganglion or it nerve fibers, radio-frequency rhizotomy) have been developed.
Another cause of facial pain is Temporomandibular Joint (TMJ) Dysfunction Syndrome. Most TMJ discomfort is temporary and can be treated with inexpensive remedies. However, some TMJ dysfunction patients are afflicted with persistent and sometimes unbearable pain. The symptoms of this chronic dysfunction include persistent pain in the facial muscles on one or both sides, a clicking or popping sensation when opening the mouth or working the jaw, recurring headaches, and difficulty chewing. Analgesics and anti-inflammatory medication may relieve the pain in some patients. Others turn to TMJ surgery in desperation.
Yet another cause of facial pain is Postherpetic Neuralgia, which is a possible complication of herpes zoster reactivation (“shingles”). The herpes zoster virus may cause chicken pox upon initial infection. When reactivated, the virus causes shingles—a painful disease characterized by eruptions along a nerve path often accompanied by severe neuralgia and a skin rash. It can affect the torso or limbs (spinal ganglia shingles) or the face (trigeminal ganglia shingles). Approximately one in five adults develops shingles, usually after age 50. For most people, shingles is an acute condition with pain typically lasting one month. However, in older patients or patients with a compromised immune system, singles can lead to postherpetic neuralgia, a very painful chronic condition in which the pain associated with the shingles persists beyond one month, even after the rash is gone. The incidence of postherpetic neuralgia is almost negligible before age 50, but at least 50% of patients older than 60 years and almost 75% beyond age 70 become affected following a shingles attack. Postherpetic neuralgia tends to improve over time without treatment. Some estimates suggest that only two to three percent of patients have pain lasting more than one year. However, since more than 60,000 new cases develop annually in the US, the collective morbidity is still substantial. Treatment of postherpetic neuralgia consists of symptomatic relief of severe pain with tricyclic antidepressants and opioids.
Epilepsy
Epilepsy is characterized by a tendency to recurrent seizures that can lead to loss of awareness, loss of consciousness, and/or disturbances of movement, autonomic function, sensation (including vision, hearing and taste), mood, and/or mental function. Epilepsy afflicts one to two percent of the population in the developed world. The mean prevalence of active epilepsy (i.e., continuing seizures or the need for treatment) in developed and undeveloped countries combined is estimated to be 7 per 1,000 of the general population, or approximately 40 million people worldwide. Studies in developed countries suggest an annual incidence of epilepsy of approximately 50 per 100,000 of the general population. However, studies in developing countries suggest this figure is nearly double at 100 per 100,000.
Epilepsy is often but not always the result of an underlying brain disease. Any type of brain disease can cause epilepsy, but not all patients with the same brain pathology will develop epilepsy. The cause of epilepsy cannot be determined in a number of patients; however, the most commonly accepted theory posits that it is the result of an imbalance of certain chemicals in the brain, e.g., neurotransmitters. Children and adolescents are more likely to have epilepsy of unknown or genetic origin. The older the patient, the more likely it is that the cause is an underlying brain disease such as a brain tumor or cerebrovascular disease.
Trauma and brain infection can cause epilepsy at any age, and in particular, account for the higher incidence rate in developing countries. For example, in Latin America, neurocysticercosis (cysts on the brain caused by tapeworm infection) is a common cause of epilepsy. In Africa, AIDS and its related infections, malaria and meningitis, are common causes. In India, AIDS, neurocysticercosis and tuberculosis, are common causes. Febrile illness of any kind, whether or not it involves the brain, can trigger seizures in vulnerable young children, which seizures are called febrile convulsions. About 5% of such children go on to develop epilepsy later in life. Furthermore, for any brain disease, only a proportion of sufferers will experience seizures as a symptom of that disease. It is therefore suspected that those who do experience such symptomatic seizures are more vulnerable for similar biochemical/neurotransmitter reasons.